Project Summary Background: Atherosclerosis is a silent disease which can progress to very late stages without highly noticeable symptoms; detecting it accurately and quickly is paramount to its management. Current imaging techniques for atherosclerosis are often untargeted or lack the resolution or signal to noise ratio necessary for accurate detection. Even state-of-the-art targeted particles for imaging typically rely on only a single targeting moiety on their surface. Our design is a platelet membrane-coated nanoparticle, a material which has multiple pathways for binding to atherosclerotic sites, and would give multiplex targeting. Platelets naturally have an intimate relationship with the development of plaque at inflamed endothelium sites, and quicken the progression of atherosclerosis. We can take advantage of this natural property to design carriers with the intrinsic properties of platelets, which will illuminate atherosclerotic sites at high specificity and sensitivity. Aims: Aim 1: Test binding of PNPs to various indicators of atherosclerosis in vitro and ex vivo. Aim 2: Evaluate the detection of atherosclerotic regions in vivo using dye loaded PNPs. Aim 3: Investigate translational ability of PNPs as a clinical imaging agent using iron oxide platelet membrane-coated nanoparticles. Conclusion: The first two aims will verify that the surface of platelet membrane, with all the receptors and integrins intact, and coated onto the surface of particles, will target and bind to atherosclerotic sites. The third aim will confirm that this platform can be made clinically relevant for use in humans by the coating of an iron oxide nanoparticle with platelet membrane. Our hypothesis is that by utilizing the natural biomolecules and receptors present on the surface of activated platelets, and coating them onto the surface of nanoparticles, we can design multivalently-binding contrast agent particles. This is a clinically relevant system which could aid MR imaging in patients with cardiovascular disease.